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PubMed1996

Reversible prolonged skin bleeding time in acute gastrointestinal bleeding presumed due to NSAIDs.

The purpose of this research was to look for a possible mechanism whereby NSAIDs, and particularly ASA, might cause gastrointestinal bleeding. A total of 34 hospitalized GI bleeders and 29 age- and sex-matched controls were studied. Skin bleeding time (SBT) was measured within 6 h of coming to hospital and before any blood products were given. All patients and controls were questioned regarding current NSAID use. This history was supplemented by estimation of serum salicylate and of platelet cyclooxygenase activity to detect unreported current aspirin (ASA) use. Various aspects of platelet function were also tested by lumiaggregation in 28 controls and, after recovery, in 27 of the bleeders. Of 34 bleeders, 26 bled from the upper GI tract, (13 from peptic ulcer) and eight from the lower GI tract, 30 (88%) had a current intake of NSAIDs and of these 22 (73%) used ASA, some in combination with other NSAIDs, whereas 12 of 29 controls were using NSAID's, 11 of which were ASA. SBT in the bleeders was 9.0 +/- 1.02 min versus 4.8 +/- 0.42 min in the controls (p < 0.001). SBT measured 6.6 days later in 28 bleeders was 4.7 +/- 0.22 min (p < 0.0006), and of those tested after recovery all but one had fallen to 6.5 min or less. None had any residual constitutional platelet abnormalities as tested by lumiaggregation. By logistic regression, NSAID intake was strongly associated with prolonged SBT to > 6 min (odds ratio [OR], 16.7; p < 0.0002), whereas NSAID intake (OR 14.6; p < 0.0003) and SBT > 6 min (OR 1.8; p < 0.005) contributed to a bleeding outcome. Almost 90% of GI bleeders had recently consumed NSAIDs, mostly ASA, on an average 15 h before onset of bleeding. Although most of the nonbleeders who had used NSAIDs did not have a prolonged SBT, most of the bleeders who used NSAIDs had an abnormal elevation of SBT, suggesting a possible mechanism for GI bleeding. Retesting approximately 7 days after recovery from bleeding showed normalization of the SBT, indicating that the defect was transient and spontaneously reversible.

Acute Disease↗
PubMed2005

Immunologic benefits of longer graft in rat allogenic small bowel transplantation.

BACKGROUND: The effect of graft length on rejection reaction in small bowel transplantation (SBT), which is poorly understood, is tested using rat allogenic SBT models with a short course of tacrolimus. MATERIALS AND METHODS: Inbred Brown Norway rats (major histocompatibility complex: RT1) and Lewis rats (RT1) were used as donors and recipients, respectively. The intestinal tract of the recipient was partially or totally replaced by segmental (15 cm) or whole (70 cm) donor intestine, using two different SBT models. With tacrolimus treatment (0.64 mg/kg per day, 0-13 postoperative days, intramuscularly), recipients' body weights and their survival were evaluated. To compare the extent of peripheral chimerism, donor passenger leukocytes were followed using flow cytometry with a donor-specific monoclonal antibody, OX-27. For the periodical histologic analysis, heterotopic SBT and protocol biopsies of the graft were also performed with short or long intestinal grafts. RESULTS: In a classical Monchik and Russell orthotopic SBT model, whole SBT recipients survived more than 60 days. However, all of the allogenic segmental SBT recipients died within 14 days without histologic sign of graft rejection. In the modified orthotopic SBT model using a cuff technique without systemic clamping, all recipients with segmental allograft survived longer than 29 days. However, recipients with whole graft tended to survive longer than those with segmental graft. The suffering period, lasting from the onset of rejection to death, was significantly shorter in the segmental group than in the whole group. Flow cytometric analysis showed that recipients with whole intestinal grafts had significantly higher ratio of donor passenger leukocytes in peripheral blood. Histologic studies of the protocol biopsies showed that the shorter graft tended to be more severely rejected than the longer graft. CONCLUSIONS: We have demonstrated experimentally that long intestinal grafts have immunologic advantage over short grafts.

Animals↗
PubMed1981

Prediction of the physiological dead space/tidal volume ratio during anaesthesia/IPPV from simple pre-operative tests.

It can be shown that the assumption of an arbitrary value for VDphys/VT during IPPV can lead to unacceptable degrees of hypo- or hyperventilation. We investigated 33 adult patients scheduled for major non-thoracic surgery, to see if any simple tests could be used to predict VDphys/VT during anaesthesia/IPPV. Fifteen were smokers and 18 non- or ex-smokers. The tests were spirometry, and the single breath tests for CO2 and for N2 (SBT-CO2: SBT-N2). Patients were ventilated during anaesthesia with a Servo Ventilator 900 B, and SBT-CO2 was recorded from a CO2 Analyzer 930. During anaesthesia/IPPV, smokers had significantly greater VDphys/VT (0.40 +/- 0.10 vs. 0.31 +/- 0.07 [P less than 0.01]), and they had more steeply sloping phase IIIs of SBT-CO2 (P less than 0.01) than non- and ex-smokers. For smokers, VDphys/VT was correlated to age (r = 0.75, P less than 0.01), to the slope of phase III of both SBT-CO2 and SBT-N2, and to the ratio of FEV% to its predicted value. For non- and ex-smokers, only one variable, efficiency, describing the shape of SBT-CO2, was correlated to VDphys/VT (r = 0.53, P less than 0.05). Pre-operative prediction of VDphys/VT based on age, smoking history, and SBT-CO2 can reduce the uncertainty in estimating VDphys/VT and therefore ventilatory requirements. It appears to offer the greatest benefits amongst smokers, who show a large variation in VDphys/VT.

Age Factors↗
PubMed1992

[Long-term medication with acetylsalicylic acid--a problem in regional anesthesia?].

In patients medicated with acetylsalicylic acid (ASA) and undergoing regional anaesthesia there is a risk of traumatically induced haematoma, particularly near the spinal cord. The increased bleeding tendency following aspirin administration is due to a change in thrombocyte aggregation caused by irreversible inhibition of prostaglandin synthesis. In order to assess the bleeding risk, it was investigated whether and how much subaqueous bleeding time (SBT) and aggregation inhibition (AGI) change under low-dose medication, and when these values return to normal after the end of administration. RESULTS. 1. SBT increased significantly with daily ASA medication of 100 mg or of 300 mg. However, only 4.5% of the values measured were within a pathologic range. After discontinuation of the medication SBT significantly dropped on the 2nd day, reaching the initial level on the 4th day at the latest. 2. AGI was significantly reduced, to 20% of the normal value. Depending on the dosage, the 100-mg group reached full aggregation capacity on the 4th day and the 300-mg group on the 7th day following discontinuation of medication. 3. AGI returned to normal 2-3 days later than SBT. CONCLUSIONS. 1. In the case of pathologically increased values (greater than 6 min), the determination of SBT may indicate an increased bleeding risk. 2. If SBT is within the normal range during or shortly after ASA administration, thrombocytic function is still disturbed. Whether there is a correlation between inhibition of thrombocyte aggregation and the occurrence of spinal haematomas is not yet known. 3. In view of these results, the effect of ASA should be investigated by determining SBT prior to scheduled regional anaesthetic procedures near the spinal cord. 4. If SBT is increased (greater than 6 min) and regional anaesthesia near the spinal cord is indicated, the procedure involving the slightest trauma (spinal anaesthesia) should be chosen [31]. Careful postoperative follow-up (1-2 days) should be guaranteed with regard to neurological disorders.

Adult↗
PubMed1989

[Effects of sulbactam on the activity of cefoperazone against various clinical isolates].

Sulbactam/Cefoperazone (SBT/CPZ) have been used in clinical infusion at ratios of 1:1 and 1:2 in Japan and U.S.A., respectively. After an administration of these drugs as a 1:1 parenteral formulation, the ratio of levels of CPZ and SBT in blood was 1:1/4 to 1:1/5 for 1 to 2 hours, whereas the ratio of free, unbound drug levels was 1:1.4 to 1:1.5. In urine these drugs were excreted at a ratio between 1:1 and 1:4 during 6 hours after the infusion. Antimicrobial interaction studies using various combinations of CPZ and SBT were performed to obtain information with respect to the effect of SBT on the antimicrobial activity of CPZ in vivo and the most appropriate ratio of these drugs for the in vitro test system. Antimicrobial activities were determined using the agar dilution method and the disk diffusion susceptibility test. SBT increased the activity of CPZ against various clinical isolates tested except Enterococcus faecalis. CPZ-SBT at a fixed ratio of 1:1/5 significantly increased the antimicrobial activity of CPZ, resulting in decreases in MIC values and increases in disk inhibitory zone diameters. These drugs at ratios 1:1 to 1:3 maximized the synergistic enhancement of the activity. Therefore, a fixed ratio between 1:1/5 and 1:1 would be appropriate for the in vitro antimicrobial test system using either the agar dilution method or the disk susceptibility test. Based on pharmacokinetic data for CPZ and SBT, results of the present study on antimicrobial activity would support that the parenteral formulation of CPZ-SBT at the fixed ratios of 1:1 and 2:1 for the intravenous infusion used in Japan and U.S.A., respectively, are appropriate. The effect of SBT on the activity of CPZ was more marked against clinical isolates with greater production abilities of beta-lactamase than against those with less production abilities. SBT/CPZ, however, exerted a synergistic effect against methicillin-resistant Staphylococcus aureus without beta-lactamase production. The MIC80 of SBT/CPZ (1:1) against various clinical isolates with 10(6) CFU/ml inoculum size were as follows: S. aureus 12.5 micrograms/ml, Staphylococcus epidermis 3.13 micrograms/ml, and E. faecalis 50 micrograms/ml. Those of Gram-negative bacilli were: Escherichia coli 0.20 microgram/ml, Klebsiella pneumoniae 0.20 micrograms/ml, Proteus mirabilis 0.78 microgram/ml, Proteus vulgaris 0.78 microgram/ml, Pseudomonas aeruginosa 12.5 micrograms/ml, Serratia marcescens 25 micrograms/ml, Enterobacter spp. 3.13 micrograms/ml, Citrobacter spp. 12.5 micrograms/ml and Acinetobacter spp. 0.78 microgram/ml.

Bacteria↗
PubMed1988

[Pharmacokinetic and clinical studies of sultamicillin granule in the pediatric field].

Sultamicillin (SBTPC) is a combined drug of ampicillin (ABPC) and sulbactam (SBT) which is an inhibitor of beta-lactamase, in a clinical form of tosylate with equivalent molecules in ester linkages. A tablet form of this combined drug has been released since July, 1987 in Japan and now a granular form for pediatric patients has been developed. Hence, the granular form of SBTPC was administered to 6 boys (age: 8 years 5 months-11 years 5 months) to determine plasma and urinary concentrations of the drug and its urinary recovery-rates. The dose of 10 mg/kg or 15 mg/kg was given orally just after meal to 3 boys. To study clinical and bacteriological effects of this drug, a mean daily dose of 27.1 mg/kg divided 2-4 times a day was administered for 9 days on the average to a total of 57 cases with pharyngitis (5), tonsillitis (5), laryngitis (1), bronchitis (1), pneumonia (8), scarlet fever (1), typhoid fever (1), impetigo (16), furuncle (2), abscess (6), lymphadenitis (1) and urinary tract infection (10) except 2 cases which were unevaluable for clinical effects. MICs of 7 drugs (SBTPC, ABPC, SBT, methicillin (DMPPC), cloxacillin (MCIPC), cephalexin and cefaclor) against 12 of 22 strains isolated from patients with infections of skin and soft tissue were determined with inoculum-sizes of 10(8) and 10(8) CFU/ml to study beta-lactamase producing activities. Adverse reactions and abnormal effects on laboratory test values attributable to this drug were studied in patients including dropped-out cases. The results obtained are summarized as follows. 1. Mean plasma peak levels of ABPC and SBT were observed at 1 hour after administration in both of the 10 mg/kg and the 15 mg/kg groups with values of 2.34 and 5.57 micrograms/ml for ABPC and 1.87 and 4.66 micrograms/ml for SBT, respectively. Mean concentrations of SBT were lower than those of ABPC in both groups and individuals. Dose-responses in plasma levels and AUCs were observed in both groups. Mean half-life values of ABPC and SBT in the 2 groups were 1.93 and 1.12 hours for ABPC and 1.97 and 1.22 for SBT, respectively. Mean half-life values for ABPC and SBT were similar in each group and this tendency was also seen among individuals.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1984

[Basic and clinical evaluation of sulbactam/cefoperazone in the field of pediatrics].

Sulbactam (SBT) in a novel beta-lactamase inhibitor from Pfizer and combined with cefoperazone (CPZ) ina 1:1 ratio (SBT/CPZ). Fundamental and clinical studies on SBT/CPZ were executed. The antibacterial activity of SBT/CPZ was compared with those of SBT, CPZ and CEZ against clinical isolates of S. aureus and E. coli which were not susceptible to CEZ. SBT alone did not show any activity against S. aureus, MICs against all strains were over than 100 micrograms/ml on the inoculations of undiluted and 100-fold diluted specimen. CPZ showed MICs over than 100 micrograms/ml against approximately 70% of the isolates on the undiluted inoculation, and on the 100-fold diluted inoculation, the MIC50 and MIC70 were 12.5 micrograms/ml and 100 micrograms/ml, respectively. SBT/CPZ showed better activity than CPZ by 2-8 folds against the strains highly resistant to CPZ; the MIC50 on the undiluted inoculation was 50 micrograms/ml. Against E. coli, the characteristic of SBT/CPZ was shown more clearly. The MICs of CPZ were over than 100 micrograms/ml against approximately 70% of the isolates on the undiluted inoculation, but SBT/CPZ showed MIC50 at 25 micrograms/ml. On the 100-fold diluted inoculation, SBT/CPZ was 4 approximately 8-fold superior than CPZ against strains on which MICs of CPZ were over than 12.5 micrograms/ml. Serum levels were determined by a bolus intravenous injection and by intravenous drip infusion of 10, 20, 40 mg/kg of SBT/CPZ. When administered by a bolus injection, the peak level was seen at 30 minutes in most patients: 8.7, 14.7 or 27.0 micrograms/ml of SBT and 30.1, 42.5 or 76.4 micrograms/ml of CPZ were detected with the 3 different doses. These levels were dose-dependent, and decreased slowly to 0.3, 0.3 or 0.3 micrograms/ml of SBT and 2.9, 2.8 or 3.3 micrograms/ml of CPZ at 6 hours after administration. Half-lives were 1.39, 1.20 or 0.98 hour for SBT and 1.77, 1.59 or 1.42 hours for CPZ. The same 3 doses were given by intravenous drip infusion. The peak levels obtained at the end of infusion (1 hour after initiation of infusion) were 15.3, 14.4 or 43.2 micrograms/ml for SBT and 33.4, 38.2 or 104.2 micrograms/ml for CPZ, respectively. The levels were somewhat low in 20 mg/kg group. After the end of infusion, these levels decreased fairly rapidly, and after 6 hours almost the same levels of 0.4, 0.5 or 0.3 micrograms/ml for SBT and 1.4, 3.9 or 3.3 micrograms/ml for CPZ were detected.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗
PubMed2001

Cytologic identification of serous neoplasms in peritoneal fluids.

BACKGROUND: Recognition of serous neoplasms in peritoneal fluids and their subclassification into serous borderline tumors (SBT) and serous carcinomas (SCA) may be difficult. The objective of this study was to determine whether morphologic criteria can distinguish reactive mesothelial cells (RM), SBT, and SCA (grades 1-3) in peritoneal fluids. METHODS: A blinded review of 42 peritoneal fluids from 40 patients with histologically confirmed RM (n = 10 patients), SBT (n = 7 patients; 3 with primary ovarian tumors and 4 with primary peritoneal tumors), and SCA (n = 23 patients; 7 with grade 1 tumors, 6 with grade 2 tumors, and 10 with grade 3 tumors; 12 with primary ovarian tumors and 11 with primary peritoneal tumors) evaluated papillae presence and size, intercellular windows, group contours, dyshesion, nuclear atypia, size and overlap, cell size, and nucleoli and nuclear-to-cytoplasmic ratios. From these parameters, specimens were classified as RM, SBT versus grade 1 SCA, or grade 2 SCA versus grade 3 SCA. RESULTS: RM were identified as groups of small cells with minimal nuclear atypia and overlap, intercellular windows, and irregular group borders without papillae. No features differentiated SBT from grade 1 SCA. Grade 2 and 3 SCA showed more nuclear atypia and overlap with larger nuclei and cells. Thirty-nine of 42 specimens (95%) were correctly identified as RM or serous neoplasm. Two SBT specimens and one grade 1 SCA specimen were overcalled, and three SCA specimens (two grade 2 and one grade 3) were undergraded. CONCLUSIONS: The distinction of RM from serous neoplasms in peritoneal fluids is possible in most patients by examination of cell group architecture, nuclear atypia, and nuclear size. Differentiation of SBT from grade 1 SCA is not reliable, meriting a differential diagnosis. Most high-grade SCA specimens can be identified by increased nuclear atypia, overlap, and size.

Adult↗
PubMed1999

The neuropathology of intestinal failure and small bowel transplantation.

The aim of this study was to elucidate the neuropathological substrate of intestinal failure before and after small bowel transplantation (SBT). Retrospective analysis of complete autopsy or brain biopsy specimens of 17 patients with intestinal failure (12 children and 5 adults) were studied. Patients were divided into two groups. Group I (transplanted group; n = 13) included those patients who underwent intestinal transplantation under tacrolimus and steroids immunosuppressive therapy. Group II (control group) included 4 children with intestinal failure who were candidates for SBT and died while awaiting an intestinal allograft. Central nervous system (CNS) abnormalities were seen in 92% of the SBT recipients and in 100% of SBT candidates. The neuropathological lesions of SBT recipients included: (a) vascular lesions: global brain ischemia, infarcts, intracranial hemorrhage and edema (7 children/2 adults; 69%); (b) cerebral atrophy (6 children; 46%); (c) Alzheimer type II gliosis (5 children/4 adults; 69%); (d) infection (3 patients; 23%) due to cytomegalovirus (1 child), Aspergillus fumigatus (1 adult) and progressive multifocal leukoencephalopathy (PML)-like (1 adult); (e) Epstein-Barr virus-related cerebral post-transplant lymphoproliferative disorder (2 children; 15%); and (f) central pontine and extrapontine myelinolysis (1 child; 7.5%). The neuropathological lesions of SBT candidates were Alzheimer type II astrocytosis (4 patients), vascular changes (4 patients), brain atrophy (4 patients) and cerebral candidiasis (1 patient). CNS vascular, metabolic and infectious pathology are significant causes of morbidity and mortality in patients suffering intestinal failure, both before and after SBT. Brain atrophy was a frequent finding and may be related to nutritional and developmental inadequacy of long-term total parenteral nutrition.

Adult↗
PubMed1993

HLA class I sequence-based typing.

HLA oligogenotyping has been used successfully to characterize most phenotypically undetectable variants of class II genes. Limitations inherent to the class I system have, however, complicated the application of this and other molecular approaches to HLA class I typing. We have previously shown that HLA class II polymorphism can be analyzed by a SBT approach. Here we present a class I-SBT strategy that provides complete sequence information for the two most polymorphic exons of the HLA-A, -B, and -C alleles. HLA class I SBT is based on direct sequencing of PCR-amplified HLA-A, -B, and -C cDNAs and requires a total of six cDNA -PCR-sequencing reactions (two per locus) and 13 different oligonucleotides. Each combination of oligonucleotides per reaction results in locus-specific sequence ladders and allows identification of both alleles in heterozygotes. Application of HLA-A, HLA-B, and HLA-C SBT to 26 homozygous and 32 serologically heterozygous samples has resulted in the identification of 24 novel class I nucleotide sequences encoding 17 new major histocompatibility complex class I products. An unexpected high degree of heterogeneity was found at the HLA-C locus with 14 novel sequences. Although there was a good correlation between the serologic phenotypes and SBT results, HLA-C SBT of most HLA-C serologically homozygous samples (heterozygous for HLA-A and/or -B) revealed heterozygozity (six of eight). SBT, the first molecular typing approach that has been generalized to both class I and class II genes, may be of special interest in applications demanding high sensitivity and specificity, such as in paternity testing or in the evaluation of the effects of sequence allelism in the outcome of unrelated bone marrow transplantation.

Alleles↗
PubMed2006

Does sedation practice delay time to extubation?

UNLABELLED: Criteria for performing a spontaneous breathing trial (SBT) have not been evaluated in controlled trials. An important component of these criteria is neurological status. The objective of this study was to evaluate whether physicians take mental status into consideration before performing an SBT in mechanically ventilated patients. METHODS: This was a prospective, observational study which included 355 mechanically ventilated patients. Daily assessments were made of whether the patients met criteria for performing a SBT. On the day a patient met the criteria, the level of sedation was evaluated using the Glasgow Coma Scale as modified by Cook and Palma (GCS-Cook) and it was registered whether or not the physician carried out an SBT. RESULTS: Two hundred and four patients (57%) underwent an SBT on the day they met the criteria (cohort 1) and in 151 patients (cohort 2) the SBT was delayed a median time of 1 day (interquartile range 1-2). There were differences in the GCS-Cook score on the day the criteria were met for performing an SBT (mean 13+/-3 points in cohort 1 versus 9+/-3 points in cohort 2; P<0.001). There were differences (P<0.001) between the cohorts in days of intubation and length of stay in the intensive care unit. CONCLUSIONS: Neurological status/level of sedation is a factor in the decision whether or not to perform a spontaneous breathing trial.

APACHE↗
PubMed2005

Piperacillin-sulbactam versus piperacillin-tazobactam: a multicentre, randomised, single-blind, controlled clinical trial.

The objective of this study was to compare the efficacy and safety of piperacillin-sulbactam (PIP-SBT) and piperacillin-tazobactam (PIP-TAZ) in the treatment of bacterial respiratory and urinary tract infections. A randomised, single-blind, controlled clinical trial was performed. Differences in clinical efficacy, bacteriology and safety between the two groups were subjected to statistical analysis, including intent-to-treat (ITT) analysis. A total of 215 cases were enrolled, with 203 complete cases (99 PIP-SBT, 104 PIP-TAZ). A total of 209 cases (103 PIP-SBT, 106 PIP-TAZ) were included in the ITT analysis and a total of 212 cases (104 PIP-SBT, 108 PIP-TAZ) were included in the safety analysis. Overall efficacy rates of PIP-SBT and PIP-TAZ were 93.2% and 93.4%, respectively. Overall bacterial eradication rates of the two groups were 95% and 97.59%, respectively. Among the PIP-SBT group, eight patients (7.69%) had adverse events, including four probable drug-related events. Among the PIP-TAZ group, nine patients (8.33%) had adverse events, including one definitely drug-related and four probable drug-related events. All differences between the two groups were insignificant. PIP-SBT could be a suitable replacement for PIP-TAZ in the therapy of community-acquired respiratory and urinary tract infections caused by beta-lactamase-producing bacterial isolates.

Adult↗
PubMed1997

Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats.

Effects of small bowel transplantation (SBT) on ileal motility are unknown. The aim of the present study was to investigate changes in spontaneous contractile activity and sensitivity to cholinergic and adrenergic agents in the ileal circular muscle after SBT in rats. Orthotopic SBT was performed in syngeneic rats to avoid immune phenomena. Distal ileal circular muscle strips from rats one week (N = 10) and eight weeks (N = 10) after SBT were stretched to optimal length (Lo), and basal spontaneous activity at Lo was measured. Dose-response experiments to the cholinergic agonist bethanechol (Be, 10(-8)-10(-4) M) were performed in the presence of tetrodotoxin (TTX, 10(-6) M) and to the adrenergic agonist norepinephrine (NE, 10(-8)-10(-4) M) with or without TTX. ED50 (negative log of drug-concentration that induced 50% effect) was calculated. We also studied rats with selective jejunoileal ischemia/ reperfusion, intestinal transection/reanastomosis, naive controls, and sham operated controls (N > or = 8/group). Spontaneous basal activity did not differ among groups. Sensitivity to Be was not different in rats after SBT or in other groups compared to control tissue. After SBT, hypersensitivity to NE was shown by a significant increase of ED50 at one and eight weeks after SBT (5.1 +/- 0.3 vs 6.2 +/- 0.4 and 6.2 +/- 0.2, respectively; P < 0.05) regardless of the presence of TTX. No hypersensitivity was observed after ischemia-reperfusion intestinal transection-reanastomosis, or sham operation. It is concluded that ileal hypersensitivity to NE was related to the extrinsic denervation obligated by the transplantation procedure, possibly mediated through an increase in number of receptors on smooth muscle, not on the enteric nerves.

Adrenergic Agonists↗
PubMed2002

Serous borderline tumors of the ovary: a long-term follow-up study of 137 cases, including 18 with a micropapillary pattern and 20 with microinvasion.

The natural history of serous borderline tumors (SBTs) of the ovary varies considerably. A group of investigators have proposed that a small subset of SBTs with a micropapillary architecture and an allegedly higher incidence of invasive peritoneal implants should be designated "micropapillary serous carcinomas." Based on the overall favorable prognosis of the nonmicropapillary SBTs, these investigators have recommended abandoning the borderline category of serous tumors, restricting them to benign (benign and typical SBTs) and malignant types; other investigators, however, are in favor of retaining the original grouping, designating borderline tumors with a micropapillary pattern as such instead of designating them carcinomas. We have reviewed the clinicopathologic records of 137 patients with ovarian SBTs and obtained follow-up information on 106 of them ranging from 1 to 18 years (mean 7 years). Of the 21 patients with stage I tumors who had conservative surgical treatment, only two (9.5%) were subsequently found to have tumor in the contralateral ovary. Both were successfully managed by reoperation alone. Forty-five stage I patients had procedures that included bilateral oophorectomy, and two of them (4.4%) had a pelvic recurrence, which was fatal in one patient (whose tumor had been understaged) and occurred on multiple occasions in the other patient, finally transforming into invasive carcinoma; that patient survived. Of the 45 stage II-IV patients, only the six (13%) with invasive implants had an unfavorable outcome: three died of tumor (from 7 to 9.3 years), and the other three were alive with progressive disease from 5 to 10 years. Solid epithelial nests or small papillae surrounded by clefts and micropapillary architecture were found more often in invasive than in noninvasive implants. However, the only feature specifically associated with a poor outcome was obvious destructive invasion of the underlying tissue. Among the 137 SBTs, we identified 18 cases of serous borderline tumors with a micropapillary pattern (SBT-MP) (so-called "micropapillary carcinoma") and 20 cases of SBT with microinvasion (SBT-Minv) (three of which were also micropapillary). We compared the two groups of tumors with the remaining 102 cases of typical SBTs (which lacked micropapillary pattern and microinvasion). Of the 17 patients with SBT-MP and follow-up data, only the one patient with invasive implants had an unfavorable outcome; similarly, of the two patients with SBT-Minv and an unfavorable outcome, one had invasive implants and the other had been incompletely staged. SBTs have a very favorable prognosis, but complete surgical staging and prolonged follow-up are advised because pelvic recurrence and occasionally transformation to invasive carcinoma may occur. Designation of SBTs as "atypical proliferative tumors" is not recommended because it discourages complete surgical staging and follow-up. Advanced stage tumors with noninvasive implants are common, characteristically behave in a benign fashion, and can be safely treated conservatively. The rare SBTs associated with invasive implants are almost always fatal. SBT-MP and SBT-Minv are much closer in their biologic behavior to SBTs than to serous carcinomas. The micropapillary pattern alone does not imply an unfavorable prognosis; only micropapillary tumors associated with invasive implants behave aggressively.

Adolescent↗
PubMed1994

A small test of a sequence-based typing method: definition of the B*1520 allele.

Santamaria et al. (Human Immunology 1993 37: 39-50) describe a method of sequence-based typing (SBT) for HLA-A, B and C alleles said to give "unambiguous typing of any sample, heterozygous or homozygous, without requiring additional typing information". From SBT analysis, which involves determination of partial sequences of mixed alleles, these investigators reported that cell lines KT17 (HLA-B35,62) and OLGA (HLA-B62) from the reference panel of the 10th International Histocompatibility Workshop express novel variants of HLA-B15 (B1501-MN6) and HLA-B35 (B3501-MN7) respectively. To study further the novel alleles, we cloned and sequenced full-length HLA-B cDNA clones isolated from the KT17 and OLGA cell lines. We find that KT17 expresses B*3501, as assigned by SBT, and B*1501, the common allele encoding the B62 antigen. We were unable to confirm that KT17 expresses the novel B1501-MN6 variant identified by SBT. For OLGA our analysis confirms the partial sequences obtained by SBT. Thus OLGA expresses B*1501 and a novel HLA-B allele. The complete sequence of the latter shows it is a hybrid having exons 1 and 2 in common with B*1501 and other B15 subtypes and exons 3-7 in common with B*3501 and related molecules including B*5301 and B*5801. The novel allele has been designated B*1520 because of its sequence similarity with the B15 group; furthermore, serological analysis shows that the B*1520 product does not express epitopes in common with either B35, B53 or B58. The B*1520 heavy chain has a similar isoelectric point to A*3101; B*1520 was undetected by previous applications of isoelectric focusing because B*1520 and A31 are both expressed by OLGA. In conclusion, HLA-B typing of two cell lines by cDNA cloning and sequencing gives concordant results with SBT for three of the four alleles. The cause of the discrepancy for the fourth allele is unknown, however, this finding indicates that the novel HLA-A, B and C sequences emerging from SBT studies need independent verification.

Alleles↗
PubMed2006

A non-invasive method for detection of intestinal mucositis induced by different classes of chemotherapy drugs in the rat.

BACKGROUND: The Sucrose Breath Test (SBT) is a simple noninvasive technique for the detection of small intestinal mucositis. AIM: We utilised rat models of intestinal mucositis induced by different classes of chemotherapeutic agents to broaden application of the SBT. METHODS: Mucositis was induced in rats by injection of Doxorubicin (Dox), Etoposide (Etop), Irinotecan (Irin), or Cyclophosphamide (Cy) and Etop in combination (Cy+Etop). The SBT was carried out following sucrose gavage, 72 h after chemotherapy. At kill, intestinal tissues were collected for mucositis assessments. RESULTS: SBT for controls was 16.0 +/- 0.6% (mean +/- SEM) cumulative dose at 90 min. Irin, Doxo, Etop, and Cy+Etop significantly decreased the SBT to 53%, 43%, 32% and 30% of saline control values, respectively (p < 0.01) whilst sucrase activity was correspondingly decreased to 60%, 36%, 14% and 2%. There was good concordance with histological mucositis severity in the jejunum, with median scores of 11, 19, 28 and 27. Correlations between SBT, sucrase activity, and histological severity score yielded r(2) values of 0.82. CONCLUSIONS: The SBT detected mucositis induced by the alkylating agent, anthracycline and DNA-topoisomerase inhibitor classes, facilitating the detection of small intestinal dysfunction, providing a further means to screen newly-developed drugs for intestinal side-effects.

Animals↗
PubMed1990

[Synergy between sulbactam and ampicillin or cefoperazone in antimicrobial activity against beta-lactamase producing microorganisms. Results with the use of microdilution broth method].

Antimicrobial activities of sulbactam (SBT) with ampicillin (ABPC) or with cefoperazone (CPZ), in other words, the effects of SBT, an beta-lactamase inhibitor, against beta-lactamase producing strains of clinical isolates, were studied using microdilution broth method. 1. beta-Lactamase producing strains such as Staphylococcus aureus, Branhamella catarrhalis, Haemophilus influenzae, Escherichia coli and Klebsiella pneumoniae decompose benzylpenicillin (PCG) which is one of substrates of the acid-metry disc method and show a strong reaction, while they do not decompose cefazolin (CEZ), another substrate, showing no or weak reaction. Thus, it is suspected that beta-lactamases produced by these organisms are mainly penicillinase (PCase). MIC-distributions of ABPC and CPZ against these clinical isolates which seemed to produce PCase shifted to lower MIC ranges with MIC's reduced to 1/4 or below when 0.025 to 0.39 microgram/ml of SBT was added. 2. It appears that beta-lactamase produced by Proteus vulgaris may be oxyiminocephalosporinase (CXase), because P. vulgaris showed strong reaction on CEZ, but moderate reaction on PCG in the acid-metry disc method. MIC-distribution of ABPC and CPZ against P. vulgaris shifted to a lower range with MIC's of 1/4 or below when 0.20 to 0.39 microgram/ml of SBT was added. 3. All the test strains of Pseudomonas aeruginosa showed strong reaction on CEZ but only 56% of the test strains showed reaction on PCG. It appears that the beta-lactamases which showed strong reaction on CEZ is cephalosporinase and is encoded in chromosome, while those beta-lactamase that showed strong reaction on PCG is encoded in a plasmid which was acquired secondarily by P. aeruginosa. MIC-distribution of CPZ against P. aeruginosa shifted to a lower range with MIC values of 1/2 or below with the addition of SBT at 1.56 micrograms/ml. 4. It appears that the synergy of SBT with ABPC or with CPZ against the PCase or CXase producing strains may occur in the presence of SBT at a concentration far less than that reported previously.

Ampicillin↗
PubMed1989

[Cerebrospinal fluid levels of sulbactam/ampicillin in rabbits with staphylococcal meningitis].

Concentrations of sulbactam (SBT) and ampicillin (ABPC) in the blood and cerebrospinal fluid (CSF) following an intravenous administration of SBT/ABPC at a dose of 150 mg/kg (SBT/ABPC = 1:2) were determined in 12 rabbits with staphylococcal meningitis. Drug concentrations were measured 9 times, 6 times each with intervals of 15 minutes and thereafter with intervals of 30 minutes. The results were compared with those of a group of 9 rabbits given 100 mg/kg of ABPC alone. 1. The maximum concentration of SBT in the CSF and the percentages of both the maximum concentration and the area under the concentration-time curve (AUC) of SBT in CSF vs. those in serum of the SBT/ABPC group were higher than those of ABPC and the half-life of SBT in the CSF was also longer than that of ABPC, all with significant difference. When these parameters for SBT of SBT/ABPC groups were compared with those of ABPC of the ABPC group, not much differences existed between the 2 groups except that the CSF half-life of SBT was much longer than that of ABPC. 2. The percentages of both the maximum concentration and AUC of ABPC in CSF vs. those in serum of the SBT/ABPC group were significantly lower than those of ABPC of the ABPC group. The CSF half-life of ABPC of the former group was longer than that of the latter. 3. The above results suggest that when SBT and ABPC are administered simultaneously, the penetration of ABPC into the CSF is inhibited.

Ampicillin↗